3 research outputs found
A more comprehensive and commanding delineation: Mary Shelley's narrative strategy in Frankenstein
- Publication venue
- Publication date
- 01/01/1993
- Field of study
This thesis argues that the first edition of Frankenstein challenges conventional reading by employing what Simpson in Irony and Authority in Romantic Poetry calls Romantic irony, where the absence of a stable 'metacomment' precludes an authoritative reading. The novel hints at such readings but prevents them. The insights offered by Tropp's Mary Shelley's Monster, Baldick's In Frankenstein's Shadow, Poovey's The Proper Lady and the woman writer and Swingle's, 'Frankenstein's Monster and its Relatives: Problems of Knowledge in English Romanticism' are considered, but none recognises the full implications of the instability deriving from multiple first- person narratives. Clemit's The Godwinian Navel acknowledges the novel's indeterminacy, but reads a specific ideological purpose in it. Paradise Last provides a language to describe the relationship between the monster and Frankenstein, but proves too unstable to fix identity or establish moral value. Similarly, Necessity ultimately fails to provide a stable explanation in terms of cause and effect. The status of nature shifts between foreground and background, never allowing final definition. These uncertainties destabilise knowledge which is compromised by its provisional nature: no authoritative reading is possible, yet the novel has narrative coherence. The reader is encouraged to try to develop a reading the structure prevents. The radical nature of the first edition is highlighted by comparison with the 1831 edition, which removes much of the ambivalence and gives the novel a clearer morality. The novel challenges conventional methods of deriving authority by disturbing the reader's orthodox orientation in the world around him' (Simpson) in order to afford 'a point of view to the imagination for the delineation of human passions more comprehensive and commanding than any which the ordinary relations of existing events can yield' (Mary Shelley)
Genomic reconstruction of the SARS-CoV-2 epidemic in England
- Author
- Aanensen David M
- Abnizova Irina
- Abudahab Khalil
- Adams Alexander
- Adams Helen
- Afifi Safiah
- Aggarwal Dinesh
- Ahmad Shazaad SY
- Aigrain Louise
- Alcolea Adela
- Alderton Alex
- Ali Mozam
- Alikhan Nabil-Fareed
- Allara Elias
- Allen Laura
- Amato Roberto
- Anderson Ralph
- Angyal Adrienn
- Annett Tara
- Aplin Stephen
- Ariani Cristina
- Ariani Cristina V
- Asad Hibo
- Ash Amy
- Ashfield Paula
- Ashford Fiona
- Atkinson Laura
- Attwood Stephen W
- Auckland Cressida
- Austin-Guest Siobhan
- Aydin Alp
- Baker David J
- Baker Paul
- Bala Sendu
- Balcazar Carlos E
- Ball Jonathan
- Barrett Jeffrey
- Barrett Jeffrey C
- Barrow Magdalena
- Barton Edward
- Bashton Matthew
- Bassett Andrew
- Bassett Andrew R
- Batra Rahul
- Battleday Kristina
- Baxter Chris
- Bayzid Nadua
- Beal James
- Beale Mathew
- Beaver Charlotte
- Beckett Angela H
- Beckwith Shaun M
- Bedford Luke
- Beer Robert
- Beggs Andrew
- Bellany Sam
- Bellerby Tristram
- Bellis Katherine L
- Bellis Katie
- Berger Duncan
- Berriman Matt
- Berry Louise
- Bertolusso Beatrice
- Best Angus
- Betteridge Emma
- Bevan Paul
- Bibby David
- Bicknell Kelly
- Binley Simon
- Binns Debbie
- Birchley Alec
- Bird Paul W
- Birney Ewan
- Bishop Chloe
- Bishop Jason
- Blackburn Kirsty
- Blacow Rachel
- Blakey Victoria
- Blane Beth
- Bolt Frances
- Bonfield James
- Bonner Stephen
- Bonsall David
- Boswell Tim
- Bosworth Andrew
- Boughton Nick
- Bourgeois Yann
- Bowker Sam
- Boyd Olivia
- Bradley Declan T
- Breen Cassie
- Brendler-Spaeth Timothy
- Bresner Catherine
- Breuer Judith
- Bridgett Stephen
- Bronner Iraad
- Bronner Iraad F
- Brooklyn Tanya
- Brooks Ellena
- Broos Alice
- Brown Julianne R
- Bucca Giselda
- Buchan Sarah L
- Buck David
- Buddenborg Sarah Kay
- Bull Matthew
- Burns Phillipa J
- Burton-Fanning Shirelle
- Bush Robert
- Byaruhanga Timothy
- Byott Matthew
- Caetano Catarina
- Cagan Alex
- Campbell Sharon
- Carabelli Alessandro M
- Cargill James S
- Carlile Matthew
- Carter Nicola
- Cartwright Joanna
- Carvalho Sílvia F
- Casey Anna
- Castigador Anibolina
- Catalan Jana
- Chalker Vicki
- Chaloner Nicola J
- Chand Meera
- Chand Meera
- Chapman Liz
- Chappell Joseph G
- Charalampous Themoula
- Chatterton Wendy
- Chaudhry Yasmin
- Chillingworth Tracey-Jane
- Churcher Carol M
- Clapham Peter
- Clark Gemma
- Clark Richard
- Clarke Adrian
- Clarke Catriona
- Clarke Phillip
- Cogger Benjamin J
- Cole Daryl
- Cole Kevin
- Collins Jennifer
- Colquhoun Rachel
- Connor Thomas R
- Cook Elizabeth
- Cook Kate F
- Coombes Jason
- Coppola Maria
- Corden Sally
- Cormie Claire
- Cornell Linda
- Cornwell Clare
- Cortes Nicholas
- Corton Craig
- Cotic Marius
- Cotton Seb
- Cottrell Simon
- Coupland Lindsay
- Cox Alison
- Cox MacGregor
- Crackett Abby
- Craine Noel
- Cranage Alison
- Craven Harriet
- Craw Sarah
- Crawford Liam
- Crawford Mark
- Cross Aidan
- Crown Matthew R
- Crudgington Dorian
- Cumley Nicola
- Curran Martin D
- Curran Tanya
- Cutts Tim
- da Silva Filipe Ana
- Dabrera Gavin
- Dabrowska Monika
- Darby Alistair C
- Davidson Rose K
- Davies Alisha
- Davies Matt
- Davies Robert
- Davies Robert M
- Davis Thomas
- Dawson Joseph
- Day Callum
- de Angelis Daniela
- De Lacy Elen
- De Maio Nicola
- de Oliveira Martins Leonardo
- de Silva Thushan I
- Debebe Johnny
- Densem Aiden
- Denton-Smith Rebecca
- Dervisevic Samir
- Dewar Rebecca
- Dey Jayasree
- Dias Joana
- Dibling Thomas
- Dobie Donald
- Dockree Cat
- Dodd David
- Dogga Sunil
- Dorman Matthew
- Dorman Matthew J
- Dougan Gordon
- Dougherty Martin
- Dove Alexander
- Downing Fatima
- Drummond Lucy
- Drury Eleanor
- du Plessis Louis
- Duckworth Nichola
- Dudek Monika
- Durham Jillian
- Durrant Laura
- Easthope Elizabeth
- Eastick Kirstine
- Easton Lisa J
- Eccles Richard
- Eckert Sabine
- Edgeworth Jonathan
- Edwards Sue
- El Bouzidi Kate
- Eldirdiri Sahar
- Ellaby Nicholas
- Elliott Scott
- Ellis Pete
- Eltringham Gary
- Ensell Leah
- Erkiert Michelle J
- Essex Sarah
- Evans Cariad
- Evans Johnathan M
- Everson William
- Fairley Derek J
- Fallon Karlie
- Fanaie Arezou
- Farr Ben
- Farr Ben W
- Fearn Christopher
- Feltwell Theresa
- Fenton Michael
- Ferguson Lynne
- Ferrero Marcella
- Fina Laia
- Flack Neil
- Flaviani Flavia
- Fleming Vicki M
- Fordham Howerd
- Forrest Sally
- Forsythe Grace
- Foster-Nyarko Ebenezer
- Foulkes Benjamin H
- Foulser Luke
- Fragakis Mireille
- Frampton Dan
- Francis Matt
- Francois Sarah
- Fraser Audrey
- Fraser Christophe
- Freeman Adam
- Freeman Timothy M
- Fryer Helen
- Fuchs Marc
- Fuller William
- Funk Sebastian
- Gajee Kavitha
- Galai Katerina
- Gallagher Abbie
- Gallagher Eileen
- Gallagher Michael D
- Gallis Marta
- Galvin Anastasia
- Garcia-Casado Maria
- Gaskin Amy
- Gatica-Wilcox Bree
- Gedny Alex
- Geidelberg Lily
- Gemmell Matthew
- Georgana Iliana
- George Ryan P
- Gerstung Moritz
- Gifford Laura
- Gilbert Lauren
- Girgis Sophia
- Girgis Sophia T
- Glaysher Sharon
- Glover James
- Goater Richard
- Goldman Nick
- Goldstein Emily J
- Golubchik Tanya
- Gomes Andrea N
- Goncalves Sonia
- Gonçalves Sonia
- Gonçalves Sónia
- Goodfellow Ian G
- Goodwin Scott
- Goudarzi Salman
- Gould Oliver
- Gourtovaia Marina
- Graham Clive
- Graham Lee
- Grant Paul R
- Gray Andy
- Gray Emma
- Green Angie
- Green Luke R
- Greenaway Jane
- Gregory Richard
- Griffiths Coline
- Gu Yong
- Guerin Florence
- Guest Martyn
- Gunson Rory N
- Gupta Ravi K
- Gutierrez Bernardo
- Haldenby Sam T
- Hamilton Will
- Hamilton William L
- Hanks Hannah
- Hansford Samantha E
- Haque Tanzina
- Harris Kathryn A
- Harrison Ewan
- Harrison Ewan M
- Harrison Ian
- Harrott Alexandria
- Harry Edward
- Hart Jennifer
- Hartley John A
- Harvey Matthew
- Harvey William T
- Harvison Julia
- Hassan-Ibrahim Mohammed O
- Heaney Judith
- Heath Paul
- Hellewell Joel
- Helmer Thomas
- Henderson John H
- Hernandez-Koutoucheva Anastasia
- Hesketh Andrew R
- Hey Jessica
- Heyburn David
- Higginson Ellen E
- Hill Jack D
- Hill Verity
- Hilson Rachel A
- Hilvers Ember
- Hobbs Rhiannon
- Holden Matthew TG
- Holland Dave
- Hollis Amy
- Holmes Alison H
- Holmes Christopher W
- Holmes Nadine
- Holmes Sarah
- Hopes Richard
- Hornett Gary
- Hornsby Hailey R
- Hosmillo Myra
- Hough Nicholas
- Houlihan Catherine
- Howson-Wells Hannah C
- Hsu Sharon N
- Hubb Jonathan
- Huckle Liz
- Huckson Hannah
- Hughes Joseph
- Hughes Margaret
- Hughes Warwick
- Hughes-Hallet Lena
- Hunter Adam
- Hutchings Stephanie
- Idle Giles
- Illingworth Chris J
- Impey Robert
- Inglis Stephen
- Iqbal Sameena
- Irish-Tavares Dianne
- Iturriza-Gomara Miren
- Izuagbe Rhys
- Jackson Adam
- Jackson Ben
- Jackson Chris
- Jackson David
- Jackson David K
- Jackson Kathryn A
- Jackson Leigh M
- Jahun Aminu S
- James Keith
- James Victoria
- Jamrozy Dorota
- Jeanes Christopher
- Jeffries Aaron R
- Jeremiah Sarah
- Jermy Andrew
- John Michaela
- Johnson Kate
- Johnson Rob
- Johnston Ian
- Jones Christopher R
- Jones Hannah
- Jones Matthew
- Jones Neil
- Jones Owen
- Jones Sophie
- Joseph Amelia
- Judges Sarah
- Jung Alexander W
- Kallepally Kalyan
- Kane Leanne
- Kay Gemma L
- Kay Keely
- Kay Sally
- Keatley Jon
- Keatley Jon-Paul
- Keeley Alexander J
- Keith Alan
- Kenyon Anita
- Kermack Leanne M
- Khakh Manjinder
- Kidd Stephen P
- Kimuli Maimuna
- King Alison
- Kirk Stuart
- Kitchen Christine
- Kitchin Lucy
- Kitchman Katie
- Kleanthous Matt
- Klimekova Martina
- Knight Bridget A
- Korlevic Petra
- Koshy Cherian
- Kraemer Moritz UG
- Krasheninnkova Ksenia
- Kumziene-Summerhayes Sara
- Kwiatkowski Dominic
- Kwiatkowski Dominic
- Lackenby Angie
- Laing Kenneth G
- Lampejo Temi
- Lane Greg
- Langford Cordelia
- Langford Cordelia F
- Laverack Adam
- Lavin Deborah
- Law Katharine
- Lawniczak Mara
- Lawton Andrew I
- Le-Viet Thanh
- Lee David
- Lee Jack CD
- Lensing Stefanie
- Lensing Stefanie V
- Leonard Steven
- Letchford Laura
- Levett Lisa J
- Lewis Jonathan
- Lewis Kevin
- Lewis-Wade Amanah
- Liddle Jennifer
- Liddle Jennifier
- Liggett Steven
- Lillie Patrick J
- Lin Quan
- Lindsay Sarah
- Lindsey Benjamin B
- Linsdell Sally
- Lister Michelle M
- Livett Rich
- Lo Stephanie
- Loman Nicholas J
- Long Rhona
- Loose Matthew W
- Louka Stavroula F
- Lovell Jamie
- Lovell Jon
- Loveson Katie F
- Lowdon Sarah
- Lowe Hannah
- Lowe Helen L
- Lucaci Anita O
- Ludden Catherine
- Ludden Catherine
- Lynch Jessica
- Lyons Ronan A
- Lythgoe Katrina
- Machin Nicholas W
- MacIntyre-Cockett George
- Mack Andrew
- Mack James
- Macklin Ben
- Maclean Alasdair
- Macnaughton Emily
- Maddison Mark
- Madona Pinglawathee
- Maes Mailis
- Maftei Laurentiu
- Mahanama Adhyana IK
- Mahungu Tabitha W
- Mair Daniel
- Maksimovic Joshua
- Makunin Aleksei
- Malone Cassandra S
- Maloney Daniel
- Mamun Irfan
- Manesis Nikos
- Manley Robin
- Mansfield Jenny
- Mantzouratou Anna
- Marchbank Angela
- Mariappan Arun
- Marriott Neil
- Martin Matt
- Martincorena Inigo
- Martinez Nunez Rocio T
- Masters Kathryn McCluggage
- Mather Alison E
- Maxwell Patrick
- Mayhew Megan
- Mayho Matthew
- Mbisa Tamyo
- McCann Clare M
- McCarthy Shane
- McCarthy Shane A
- McClintock Jo
- McClure Patrick C
- McCrone JT
- McGuigan Samantha
- McHugh Martin P
- McHugh Sandra
- McKenna James P
- McKerr Caoimhe
- McManus Georgina M
- McMinn Liz
- McMurray Claire
- McMurray Claire L
- McNally Alan
- Meadows Carl
- Meadows Lizzie
- Medd Nathan
- Megram Oliver
- Menegazzo Mirko
- Merrick Ian
- Michell Stephen L
- Michelsen Michelle L
- Mirfenderesky Mariyam
- Mirza Jeremy
- Miskelly Julia
- Mobley Emily
- Moles-Garcia Emma
- Moll Robin
- Moll Robin J
- Molnar Zoltan
- Monahan Irene M
- Mondani Matteo
- Monteiro Tiago Carvalho
- Mookerjee Siddharth
- Moore Catherine
- Moore Christopher
- Moore Jonathan
- Moore Nathan
- Morcrette Helen
- Morgan Mari
- Morgan Sian
- Mori Matilde
- Morra Maria
- Morriss Arthur
- Morrow Leanne
- Moses Samuel
- Mower Craig
- Muir Peter
- Mukaddas Afrida
- Munemo Florence
- Munn Robert
- Murie Kathryn
- Murray Abigail
- Murray Darren R
- Murray Leanne J
- Mutingwende Manasa
- Myers Richard
- Nash Sian
- Nastouli Eleni
- Nathwani Claire
- Naydenova Plamena
- Neaverson Alexandra
- Nebbia Gaia
- Nelson Andrew
- Nelson Charlotte
- Nelson Rachel
- Nerou Ed
- Nguyen Thuy
- Nicholls Sam
- Nichols Jenna
- Nicholson Jon
- Nicodemi Roberto
- Nimz Tabea
- Noell Guillaume G
- Nomikou Kyriaki
- Odedra Mina
- Ohan Valeriu
- Ohemeng-Kumi Natasha
- Oliver Karen
- Olney Charles
- Ormond Doug
- Orton Richard J
- Osman Husam
- Oszlanczi Agnes
- O’Brien Sarah
- O’Grady Justin
- O’Meara Sarah
- O’Toole Áine
- Pacchiarini Nicole
- Padgett Debra
- Page Andrew J
- Palmer Steve
- Pang Yoke Fei
- Panovska-Griffiths Jasmina
- Pardubska Barbora
- Park Emily J
- Park Naomi
- Park Naomi R
- Parker Matthew D
- Parmar Aaron
- Parmar Surendra
- Partridge David G
- Pascall David
- Patel Amita
- Patel Bindi
- Patel Gaurang
- Patel Minal
- Paterson Steve
- Payne Brendan AI
- Payne Maggie
- Peacock Sharon
- Peacock Sharon J
- Pearson Clare
- Pelosi Emanuela
- Percival Benita
- Perkins Jon
- Perry Malorie
- Petersen Arabella
- Pinckert Malte L
- Platt Steven
- Plowman Deborah
- Podplomyk Olga
- Pohare Manoj
- Pond Marcus
- Pope Cassie F
- Poplawski Radoslaw
- Powell Jessica
- Poyner Jennifer
- Preston Tom
- Prestwood Liam
- Price Anna
- Price James R
- Prieto Jacqui A
- Pritchard David T
- Prosolek Sophie J
- Puethe Christoph
- Pugh Georgia
- Pusok Monika
- Pybus Oliver G
- Pymont Hannah M
- Quail Michael
- Quail Michael A
- Quick Joshua
- Radulescu Clara
- Raghwani Jayna
- Ragonnet-Cronin Manon
- Rainbow Lucille
- Rajan Diana
- Rajatileka Shavanthi
- Ramadan Newara A
- Rambaut Andrew
- Ramble John
- Rance Richard
- Randell Paul
- Randell Paul A
- Ratcliffe Liz
- Raviprakash Veena
- Rawlings Suzannah
- Raza Mohammad
- Redshaw Nicholas
- Redshaw Nicholas M
- Rey Sara
- Reynolds Joe
- Reynolds Mark
- Reynolds Nicola
- Rice Simon
- Richardson Matt
- Richter Alex
- Roberts Connor
- Robertson David L
- Robinson David
- Robinson Esther
- Robinson Katrina
- Robinson Melanie
- Robson Samuel C
- Rogan Fiona
- Rogers Hazel
- Rojo Eduardo Martin
- Rooke Stefan
- Roopra Daljit
- Rose Mark
- Rowe Will
- Roy Sunando
- Rudd Luke
- Rudder Steven
- Ruis Chris
- Rushton Steven
- Sadri Ramin
- Saeed Kordo
- Saint Callum
- Salmon Nicholas
- Samaraweera Buddhini
- Sambles Christine M
- Sanderson Roy
- Sanderson Theo
- Sanderson Theo
- Sang Fei
- Sass Thea
- Saul David
- Scher Emily
- Schwach Frank
- Schwach Frank
- Scott Carol
- Scott Garren
- Seekings Phil
- Sehmi Jasveen
- Shaaban Sharif
- Shah Divya
- Shaw Jessica
- Shelest Ekaterina
- Shepherd James G
- Sheridan Liz A
- Sheriff Nicola
- Shirley Lesley
- Sillitoe John
- Silviera Siona
- Simms Alison
- Simpson David A
- Singh Aditi
- Singleton Dawn
- Sinnott Matthew
- Sinnott Matthew
- Sivadasan Shanthi
- Siwek Bart
- Sizer Dale
- Skeldon Kenneth
- Skelton Jason
- Skvortsov Timofey
- Slater-Tunstill Joanna
- Sloan Tim J
- Sloper Lisa
- Sluga Graciela
- Smerdon Nathalie
- Smith Chris
- Smith Christen
- Smith Colin P
- Smith Darren L
- Smith James
- Smith Katie
- Smith Ken
- Smith Kim S
- Smith Louise
- Smith Michelle
- Smith Nikki
- Smith Perminder
- Smith Sean
- Smith Tina
- Smollett Katherine L
- Sneade Leighton
- Snell Luke B
- Somassa Thomas
- Soria Carmen Diaz
- Sousa Catarina
- Souster Emily
- Southgate Joel
- Sparkes Andrew
- Spellman Karla
- Spencer Chapman Michael H
- Spencer-Chapman Michael
- Spurgin Lewis G
- Spyer Moira J
- Squares Janet
- Stanley Rachael
- Stanley Robert
- Stanley William
- Stanton Thomas D
- Starinskij Igor
- Steed Claire
- Stickland Tim
- Still Ian
- Stockton Joanne
- Stonehouse Susanne
- Storey Nathaniel
- Stratton Michael R
- Strickland Michelle
- Studholme David J
- Suciu Maria
- Sudhanva Malur
- Swann Allen
- Swiatkowska Agnieszka
- Swift Emma
- Swindells Emma
- Sycamore Neil
- Symons Edward
- Szluha Suzanne
- Taha Yusri
- Taluy Emma
- Tan Ngee Keong
- Tang Julian W
- Tang Miao
- Tao Nunu
- Taylor Ben EW
- Taylor Joshua F
- Taylor Katy
- Taylor Sam
- Taylor Sarah
- Temperton Ben
- Templeton Kate E
- Thomas Claire
- Thompson Mark
- Thompson Stacey
- Thomson Emma C
- Thomson Laura
- Thomson Mark
- Thomson Nicholas
- Thornton Alicia
- Thurston Scott
- Thurston Scott AJ
- Todd John A
- Tomb Rachael
- Tong Lily
- Tonkin-Hill Gerry
- Toombs Dee
- Topping Benjamin
- Torok M Estee
- Tovar-Corona Jaime
- Tovar-Corona Jaime M
- Trebes Amy
- Trotter Alexander J
- Tsatsani Ioulia
- Turnbull Robyn
- Turtle Lance
- Twohig Katherine A
- Umpleby Helen
- Underwood Anthony P
- Ungureanu Daniel
- Uphill James
- Urbanova Jana
- Vamos Edith E
- Van Vuuren Philip Jansen
- Vancollie Valerie
- Vasylyeva Tetyana I
- Vattipally Sreenu
- Verdejo Carlos Jimenez
- Vernet Gabrielle
- Vipond Barry B
- Voak Paul
- Volz Erik
- Volz Erik M
- Vöhringer Harald S
- Walker Danielle
- Walker Matthew
- Waller Matt
- Walsh Sarah
- Wang Dennis
- Ward Gary
- Warne Ben
- Warwick-Dugdale Joanna
- Wastnedge Elizabeth
- Watkins Joanne
- Watson Louisa K
- Waugh Sheila
- Weatherhogg Charlie
- Webb Niki
- Webster Hermione J
- Weldon Danni
- Wells Alan
- Wells Eloise
- Westwick Elaine
- Westwood Luke
- Whalley Thomas
- Wheeler Helen
- Whipp Theo
- Whitehead Mark
- Whiteley Max
- Whiteley Thomas
- Whitton Georgia
- Whitwham Andrew
- Widaa Sara
- Wierzbicki Claudia
- Willford Nicholas J
- Williams Catryn
- Williams Charlotte A
- Williams Cheryl
- Williams Chris
- Williams Lesley-Anne
- Williams Mia
- Williams Rachel J
- Williams Rebecca
- Williams Thomas
- Williamson Kathleen A
- Wilson Mark
- Wilson-Davies Eleri
- Witele Eric
- Withell Karen T
- Witney Adam A
- Wolverson Paige
- Wong Nick
- Workman Trudy
- Wright Derek W
- Wright Sean
- Wright Victoria
- Wyatt Tim
- Wyllie Sarah
- Xu-McCrae Li
- Yavus Mehmet
- Yaze Geraldine
- Yeats Corin A
- Yebra Gonzalo
- Yew Wen C
- Young Gregory R
- Young Jamie
- Zamudio Marina Escalera
- Zarebski Alex E
- Zhang Peijun
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 14/10/2021
- Field of study
AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- Abd Elghafar Mohamed S.
- Abdel-Aziz Mahmoud
- Abdelrazik Marwa
- Abdollahi Hamed
- Abdullah T.
- Abecasis Goncalo
- Abedalthagafi M.
- Abel Lynn
- Abernathy C.
- Abraheem Azmeralde
- Abul-Husn Noura S.
- Acquilini D.
- Adams C.
- Adams Emma L.
- Adams K.
- Adamsara Alireza
- Adanini Olurenke
- Adeleye O.
- Adra D.
- Afilalo J.
- Afilalo M.
- Afolabi D.
- Afrasiabi Z.
- Agasou A.
- Agrawal Shruti
- Agüero D.
- Ahmad N.
- Ahmadi Saeideh
- Ahmed A.
- Ahmed Cecilia
- Akeroyd L.
- Akhtar M.N.
- Akinkugbe O.
- Aksentijevich Alexandra
- Al-Afghani H.
- Al-Awdah L.
- Alaamery M.
- Alahmadey Z.Z.
- Alaverdian D.
- Alavere H.
- Albader A.
- Albaiceta G.M.
- Albakri J.K.
- AlBardis H.
- Albeladi M.
- Albesher N.
- Albrich W.
- AlDhawi N.
- Aldridge J.
- Aleagha Afshar Etemadi
- Alexander Peter.
- Alfonso J.
- Alghamdi B.
- Alghamdi J.
- Ali A.
- Ali Altaf
- Ali I.A.M.
- Ali Syamlan
- Aliannejad Rasoul
- Aljawini N.
- AlJohani S.
- Alkwai S.
- Allan A.
- Allan E.
- Allan J.
- Alldis Zoe
- Allen L.
- Allen Meryem
- Allen Schvearn
- Allibone S.
- Allison K.S.
- Allos R.
- Ally S.M.
- AlMalik A.
- Almalki F.
- Almohammed I.
- Almutairi M.
- Alotaibi S.
- Alowayn A.M.
- Alqahtani S.
- Alqubaishi F.
- Alrashed M.
- Alshareef A.
- Alsolm E.
- Alswailm M.
- Altabaibeh A.
- Alvaro A.
- AlZahrani D.
- Amin V.
- Amirsavadkouhi Ali
- Amitrano Sara
- Anastasescu E.
- Anderson F.
- Anderson J.
- Anderson Madeleine
- Anderson Peter
- Anderson S.
- Anderson S.
- Anderson T.
- Andolfo I.
- Andretta F.
- Andreucci E.
- Andrew Angela
- Andrew B.
- Andrew Gratrix
- Andrews E.
- Andrews Shea J.
- Anedda F.
- Anemoli V.
- Annis A.
- Antcliffe David
- Antinori Andrea
- Antoni M.D.
- Anumakonda V.
- Apetri E.
- Aquino Maia
- Arabi Y.M.
- Aravindan Latha
- Arbane Gill
- Archer Katie
- Arden T.
- Arias Sonia Sousa
- Arif S.
- Armstrong Jacob
- Armstrong Lisa
- Armstrong Ruth
- Arning N.
- Arnold Sophie
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- Åsvold Bjørn Olav
- Publication venue
- Publication date
- 01/01/2022
- Field of study
Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease